Etripamil

Established in Montreal 22 years ago, Milestone Pharmaceuticals has gained its first FDA approval, winning a nod for Cardamyst, a nasal spray to treat sudden episodes of the heart racing condition paroxysmal supraventricular tachycardia (PSVT). Clearing clinical and regulatory hurdles in the development of a fast-acting nasal spray for a heart condition has given Milestone Pharmaceuticals its first FDA approval in its 22-year history.The U.S. regulator has signed off on Cardamyst (etripamil) to quell symptomatic episodes from paroxysmal supraventricular tachycardia (PSVT), which is a type of abnormal heart rhythm. Cardamyst becomes the first self-administered treatment patients can use to manage their PSVT symptoms.The calcium channel blocker is a convenient alternative to an emergency room visit, where patients receive an intravenous dose of a drug that “basically reboots your heart,” Milestone CEO Joe Oliveto said in an interview.“It’s only a few seconds but nevertheless, these people really don’t like it,” Oliveto said, adding that patients have told him receiving the IV treatment is “like a near death experience.”Nearly as traumatizing for PSVT patients are the heart racing episodes which come sporadically and without warning. Oliveto said some patients have described even just a 10-minute attack of palpitations as feeling like they had run a marathon.PSVT occurs when a short circuit rhythm develops in the upper chamber of the heart. It causes rapid heartbeat that starts and stops abruptly. The heart rate can run up to 230 beats per minute.The only treatments used to counter PSVT are prophylactics such as beta blockers, anti-arrhythmic drugs and other calcium channel blockers that are taken orally and provide mixed results in curbing the episodes.With its ability to provide potentially speedy relief, Oliveto believes  Cardamyst can give patients peace of mind and more flexibility as they plan their activities. Oliveto calls it “insurance in my pocket.”“Seventy percent of patients report anxiety even when they’re not in an event and that’s because they don’t know when an event is going to come,” Oliveto said. “Is it going to happen when I’m with my grand-kids or I’m at work at an important presentation or I’m on a plane to Europe. It’s like they’re walking on eggshells. It’s always there on their minds and the current solution is not great—a trip to the emergency department.” Results from a phase trial show that Cardamyst was twice as effective and worked three times as fast as a placebo in restoring normal heart rhythm. Of the patients on etripamil, 64% achieved termination of their PSVT compared to 31% of those on placebo.Getting that result took some time, however, after a phase 3 trial in 2020 came up short as Cardamyst failed to top placebo. After discussions with the FDA, Milestone got better test results when it allowed patients to use a second dose and adjusted to a shorter time frame (30 minutes) for measuring the success of the treatment.“The patient takes the dose, which is basically one spray in each nostril,” Oliveto said. “And if after 10 minutes, there’s no response, you take another one and that really boosted the efficacy for us to the data we have now. That gave us an extra 10 to 15% of patients who responded in that first half hour.”Milestone, which was established in Montreal, opened the fourth quarter with cash equivalents of $83 million. In a deal with RTW Investments, the company will receive $75 million in exchange for tiered royalties.The company will charge $1,649 per prescription of Cardamyst, "which aligns with net revenues to Milestone of between $500 and $1,000 per prescription,"  Lorenz Muller, chief commercial officer, said in a Monday webcast. While there are roughly 2 million people in the U.S. with PSVT, Milestone is hoping to gain approval for Cardamyst in a larger indication—atrial fibrillation with rapid ventricular response (AFib-RVR), which includes around 10 million to 12 million U.S. patients. With one nod in hand for Cardamyst, Oliveto believes a label expansion could be accomplished with one successful phase 3 trial.“PSVT opens everything up for us to be transformative. It transforms us from a development company into a commercial company,” Oliveto said. “It transforms us from a single indication to now starting the AFIB phase 3 indication.”Milestone was up more than 35% premarket Monday morning on the news.